Search Results (27)

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy. Full article

Dermatofibromas (DFs) are benign neoplasms of the dermis typically found on the extremities of young adults. In approximately 3–5% of cases, basaloid cell hyperplasia (BCH) is observed overlying DFs. BCH is characterized by the proliferation of basaloid cells within the epidermis. BCH and superficial basal cell carcinoma (BCC) share many histological features, making their differentiation challenging. It is therefore unclear if the proliferation of basaloid cells in DFs represents an inductive process or, conversely, a malignant transformation indicative of BCC. The primary objective of our study was to determine whether BCH can be distinguished from superficial BCC using histology and immunhistological techniques. The histological and immunohistochemical characteristics of 43 DF samples with overlying BCH revealed significant similarities in staining patterns with those of superficial BCC described in the literature. These findings point to the need for innovative methods, such as molecular techniques, to refine diagnostic accuracy. Full article

Background: Medullary thyroid carcinoma (MTC) is a rare malignancy derived from parafollicular C-cells, with calcitonin (Ct) as its key biomarker. While basal Ct (bCt) levels above 100 pg/mL strongly suggest MTC, intermediate elevations (10–100 pg/mL) may reflect C-cell hyperplasia (CCH) or other benign conditions, making diagnostics challenging. Although calcium stimulation testing enhances sensitivity, the optimal cut-off values and comparative efficacy of calcium gluconate (CG) versus calcium chloride (CC) remain insufficiently researched. Methods: Data on 176 patients who underwent total thyroidectomy between 2009 and 2025 were retrospectively analyzed. BCt values ranged from 10 to 100 pg/mL, and stimulated Ct (sCt) values were above 100 pg/mL. CG was used from 2009 to 2019, and CC was used from 2020 to 2025. Definitive pathohistological findings divided patients into those with MTC, CCH, or no C-cell pathology. Receiver operating characteristic (ROC) analysis identified optimal Ct thresholds for predicting MTC for each stimulatory agent. Results: Of the 176 patients, 36 (20.5%) had confirmed MTC. A bCt threshold of 31.1 pg/mL yielded 69.4% sensitivity and 87.1% specificity. For sCt, optimal cut-offs were 810.8 pg/mL for CG and 1076 pg/mL for CC. Lower thresholds (388.4 pg/mL for CG and 431.5 pg/mL for CC) improved sensitivity (≥76.9%) and negative predictive value (>91%). Conclusions: Calcium stimulation testing improves MTC detection in patients with moderate bCt elevation. Although CG showed marginally better diagnostic performance, CC remains a practical and reliable alternative, especially when higher cut-off values are considered. Early surgical intervention should be considered when sensitivity-driven thresholds are met. Full article

A 56-day trial was conducted to assess the effects of rice straw (RS) and bamboo flour (BF) on growth performance, water quality, gill histology, and the bacterial community of water and the intestine of mandarin fish (Siniperca chuatsi) in biofloc technology systems. The results showed that mandarin fish in the RS and BF groups had comparable survival rates of 100.00 ± 0.00 and 93.33 ± 3.85%; feed conversion ratios of 1.13 ± 0.02 and 1.40 ± 0.15; and weight gain rates of 112.21 ± 1.56 and 100.92 ± 6.45%, respectively. From days 11 to 56 of the farming period, the BF group was more effective than the RS group in removing total ammonia nitrogen (TAN) and NO₂⁻-N, maintaining TAN levels below 0.24 ± 0.05 mg/L. During the early stage of the experiment, the TAN level in the RS group was higher; however, with the supplementation of a carbon source, it gradually decreased and eventually stabilized at 0.13 ± 0.03 mg/L later in the farming period. The secondary gill lamella in the RS group was curved and showed hyperplasia, and the basal gill lamellae showed an increase in the volume of interlamellar cell mass in the BF group. Genes related to denitrification (narG, napA, nirS, nirK, and nosZ) and anammox showed higher expression levels in the BF group than in the RS group, although the differences were not statistically significant (p > 0.05). The results of 16S rRNA sequencing research showed that both treatment groups’ intestinal and water bacterial communities had comparable levels of richness and diversity. Pseudomonas mosselii was the dominant bacterial species in the water. In the BF group, the dominant intestinal species were Bacillus halodurans and Caldalkalibacillus thermarum, while in the RS group, the dominant species was Plesiomonas shigelloides. In conclusion, rice straw and bamboo flour are applicable in BFT systems for mandarin fish culture, with good growth performance and water quality. The BF group showed higher nitrogen removal efficiency and denitrification gene expression than the RS group. Full article

Airway basal cells from chronic obstructive pulmonary disease patients show a reduction in HOXA1 expression and generate an abnormal airway epithelium. Because the specific role of HOXA1 in airway basal cells is not known, we investigated the contribution of HOXA1 in the generation of the airway epithelium, which depends on basal cell proliferation, polarization, and differentiation. Airway stem cells were transduced with an inducible HOXA1 shRNA lentivector to knock down HOXA1 in either proliferating cells or100% confluent cells. The bronchial epithelium expresses HOXA1 near the basement membrane, likely representing basal cells. HOXA1 knockdown in proliferating basal cells attenuated cell proliferation. HOXA1 knockdown in confluent monolayers of basal cells generated an abnormal airway epithelium characterized by goblet cell hyperplasia and an inflammatory phenotype. Compared to the control, HOXA1 knockdown cells showed a decrease in transepithelial resistance, localization of occludin and E-cadherin to the intercellular junctions, reduced expression of occludin but not E-cadherin, and increased expression of TNF-α. Blocking TNF-α increased the expression of occludin in HOXA1 K/D cells. Based on these results, we conclude that HOXA1 plays an important role in cell proliferation, polarization, and differentiation, which are essential steps in airway epithelial generation. Additionally, HOXA1 may regulate occludin expression by inhibiting TNF-α expression. Full article

Dermatofibromas (DFs) represent prevalent benign fibrohistiocytic tumors, typically manifesting as solitary lesions. In the majority of cases, the clinical presentation and dermoscopic and histopathological features of DFs adhere to a characteristic profile. However, DFs may exhibit atypical clinical presentations and, more commonly, histologic attributes, posing challenges in differential diagnosis. Both DFs and basal cell carcinomas (BCCs) are frequently encountered cutaneous lesions, each characterized by distinct clinical and dermoscopic features and microscopic morphology. The simultaneous occurrence of these two entities within the same lesion is rare. DFs have been documented to form collision tumors in conjunction with a spectrum of benign and malignant lesions, encompassing not only BCC but also balloon cell nevus, squamous cell carcinoma (SCC), and melanoma. Alterations in the epidermis overlaying a DF range from simple hyperplasia to the proliferation of basaloid cells. Accurate diagnosis, leading to the complete excision of the lesion, is contingent upon the recognition of dermoscopic criteria, precluding misinterpretation as a benign lesion. We present two cases of collision tumors comprising DF and BCC. This case report underscores the paramount importance of dermoscopy and adherence to dermoscopic criteria in the assessment of collision lesions and the diagnostic process related to cutaneous malignancies. Full article

The bursa of Fabricius (BF) plays crucial roles in the goslings’ immune system. During waterfowl breeding, the presence of lipopolysaccharides (LPSs) in the environment can induce inflammatory damage in geese. Polysaccharides of Atractylodes macrocephala Koidz (PAMKs), as the main active component of the Chinese medicine Atractylodes macrocephala, have significant immune-enhancing effects. Accordingly, this study intended to investigate the effect of PAMKs on LPS-induced BF injury in goslings. Two hundred 1-day-old goslings (half male and half female) were selected and randomly divided into control, PAMK, LPS, and PAMK + LPS groups. The control and LPS groups were fed the basal diet, and the PAMK and PAMK + LPS groups were fed the basal diet containing PAMKs at 400 mg/kg. The goslings in the LPS and PAMK + LPS groups were injected intraperitoneally with LPS at a concentration of 2 mg/kg on days 24, 26, and 28 of this study. The control and PAMK groups were injected with equal amounts of saline. On the 28th day, 1 h after the LPS injection, the BF and serum were collected and analyzed for organ indices, cytokines, antioxidant indicators, and histological observations. Histological examination and HE staining demonstrated that the PAMK treatment ameliorated the LPS-induced BF atrophy, structural damage, increased cellular exudation, and reticulocyte hyperplasia in the goslings. The cytokine and antioxidant marker analyses in the BF cells demonstrated that the PAMK treatment mitigated the LPS-induced increase in the interleukin-1β (IL-1β), malondialdehyde (MDA), and inducible nitric oxide synthase (iNOS) levels, as well as the decrease in the transforming growth factor-β (TGF-β) and superoxide dismutase (SOD) activities. Further transcriptome sequencing identified a total of 373 differentially expressed genes (DEGs) between the LPS and PAMK + LPS groups. The KEGG enrichment pathway analysis showed that the DEGs were significantly enriched in the Toll-like receptor, p53, MAPK, GnRH, and ErbB signaling pathways. Among them, EREG played key roles in the activation of the MAPK, GnRH, and ErbB signaling pathways. Further research showed that the addition of PAMKs significantly inhibited the LPS-induced EREG expression, increased the cell viability, promoted the cell cycle entry into the S and G2 phases, and inhibited apoptosis. Meanwhile, PAMKs can reduce the protein expression of p-JNKs and c-FOS by inhibiting EREG. In summary, this study found that PAMKs could alleviate LPS-induced BF injury in goslings by inhibiting the expression of EREG. Full article

In homeostatic conditions, the basal progenitor cells of the esophagus differentiate into a stratified squamous epithelium. However, in the setting of acid exposure or inflammation, there is a marked failure of basal cell differentiation, leading to basal cell hyperplasia. We have previously shown that lysyl oxidase (LOX), a collagen crosslinking enzyme, is upregulated in the setting of allergic inflammation of the esophagus; however, its role beyond collagen crosslinking is unknown. Herein, we propose a non-canonical epithelial-specific role of LOX in the maintenance of epithelial homeostasis using 3D organoid and murine models. We performed quantitative reverse transcriptase PCR, Western blot, histologic analysis, and RNA sequencing on immortalized non-transformed human esophageal epithelial cells (EPC2-hTERT) with short-hairpin RNA (shRNA) targeting LOX mRNA in both monolayer and 3D organoid culture. A novel murine model with a tamoxifen-induced Lox knockout specific to the stratified epithelium (K5CreER; Lox^fl/fl) was utilized to further define the role of epithelial LOX in vivo. We found that LOX knockdown decreased the proliferative capacity of the esophageal epithelial cells in monolayer culture, and dramatically reduced the organoid formation rate (OFR) in the shLOX organoids. LOX knockdown was associated with decreased expression of the differentiation markers filaggrin, loricrin, and involucrin, with RNA sequencing analysis revealing 1224 differentially expressed genes demonstrating downregulation of pathways involved in cell differentiation and epithelial development. Mice with Lox knockout in their stratified epithelium demonstrated increased basaloid content of their esophageal epithelium and decreased Ki-67 staining compared to the vehicle-treated mice, suggesting reduced differentiation and proliferation in the Lox-deficient epithelium in vivo. Our results demonstrate, both in vivo and in vitro, that LOX may regulate epithelial homeostasis in the esophagus through the modulation of epithelial proliferation and differentiation. Understanding the mechanisms of perturbation in epithelial proliferation and differentiation in an inflamed esophagus could lead to the development of novel treatments that could promote epithelial healing and restore homeostasis. Full article

Background: Esophageal organoids from a variety of pathologies including cancer are grown in Advanced Dulbecco’s Modified Eagle Medium-Nutrient Mixture F12 (hereafter ADF). However, the currently available ADF-based formulations are suboptimal for normal human esophageal organoids, limiting the ability to compare normal esophageal organoids with those representing a given disease state. Methods: We have utilized immortalized normal human esophageal epithelial cell (keratinocyte) lines EPC1 and EPC2 and endoscopic normal esophageal biopsies to generate three-dimensional (3D) organoids. To optimize the ADF-based medium, we evaluated the requirement of exogenous epidermal growth factor (EGF) and inhibition of transforming growth factor-(TGF)-β receptor-mediated signaling, both key regulators of the proliferation of human esophageal keratinocytes. We have modeled human esophageal epithelial pathology by stimulating esophageal 3D organoids with interleukin (IL)-13, an inflammatory cytokine, or UAB30, a novel pharmacological activator of retinoic acid signaling. Results: The formation of normal human esophageal 3D organoids was limited by excessive EGF and intrinsic TGFβ-receptor-mediated signaling. Optimized HOME0 improved normal human esophageal organoid formation. In the HOME0-grown organoids, IL-13 and UAB30 induced epithelial changes reminiscent of basal cell hyperplasia, a common histopathologic feature in broad esophageal disease conditions including eosinophilic esophagitis. Conclusions: HOME0 allows modeling of the homeostatic differentiation gradient and perturbation of the human esophageal epithelium while permitting a comparison of organoids from mice and other organs grown in ADF-based media. Full article

The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air–liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial–mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells. Full article

Background: The umbilicus is a fibrous remnant located in the centre of the abdomen. Various entities may be encountered in this special anatomical location; however, little is known about their dermoscopic presentation. The aim of this study was to provide a comprehensive summary of existing evidence on dermoscopic features of umbilical lesions. Methods: Studies assessing dermoscopic images of umbilical lesions were included in this study. No age, ethnicity or skin phototype restrictions were applied. Papers assessing lesions outside of the umbilical area, lacking dermoscopic images and/or dermoscopic description and not related to the topic were excluded. Embase, Medline and Cochrane Library were searched from inception to the end of May 2023. The Joanna Briggs Institute critical appraisal tools were used to evaluate the risk of bias of the selected studies. The quality and the level of evidence of included studies were assessed according to the Oxford 2011 Levels of Evidence. Thirty-four studies reporting a total of 39 lesions met the inclusion criteria and were included in qualitative analysis. Results: A qualitative synthesis of the following entities was performed: melanoma, nevi, basal cell carcinoma, fibroepithelioma of Pinkus, Sister Mary Joseph nodule, mycosis fungoides, dermatofibroma, endometriosis, epidermal cyst, granuloma, intravascular papillary endothelial hyperplasia, lichen planus, omphalolith, seborrheic keratosis, and syringoma. Conclusions: Dermoscopy is a non-invasive technique that may be useful in the differential diagnosis of umbilical lesions. The main limitations of this study were lack of a high level of evidence in the studies and the lack of uniformity in applied dermoscopic terminology between included studies. Full article

An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process. Full article

The alteration of progenitor/stem cells present in the airway epithelium has been observed in patients with COPD. Smoking exposure induces remodeling patterns in bronchial progenitor cells (BPCs), encompassing squamous metaplasia, hyperplasia of basal and of mucus-secreting cells, and the depletion of ciliated and non-mucous secretory cells. Our aim was to assess the expression of p63 and vimentin as potential markers of airway remodeling and the regulation of stem cell populations in obstructive and neoplastic lung disease patients. A retrospective single-center observational study was conducted, including patients undergoing bronchoscopy with bronchial biopsies for suspected lung cancer. p63 and vimentin expression were evaluated via immunohistochemical analysis. There were 25 patients, of which 21 with COPD were included, and 17 were diagnosed with lung cancer. We observed that FEV1% was negatively correlated with p63+ basal cell number (r = −0.614, p = 0.019) and positively correlated with vimentin expression (r = 0.670; p = 0.008). p63 was significantly higher in biopsies from the trachea and main bronchi compared to more distal areas (p = 0.040), whereas vimentin was prevalent in the more distal areas (p = 0.042). Our preliminary data suggest the initial evidence of structural changes in BPCs among patients with COPD and lung cancer. Further research efforts are warranted to investigate additional morphologic and functional respiratory parameters in these patients. Full article

Objectives: Endometriosis (EM) is the presence of endometrial tissue outside the uterus. This study aimed to examine the effects of quince gel and hesperidin treatment on uterine tissue in an experimental endometriosis model. Materials and Methods: Thirty-two rats were categorized into four groups as sham, EM, EM+quince gel (QG), and EM+QG+Hesperidin (HES). The endometriosis (EM) model was induced with surgical intervention. Estradiol benzoate (EB) was used to induce endometrial hyperplasia. In the EM group, EB was given to rats for 7 days. The EM+QG group received 2 cc QG for 21 days. HES treatment was given for 21 days after EM induction. At the end of the experiment, blood was taken from the animals and the serum total antioxidant status (TAS) and total oxidant status (TOS) values were studied. Uterine tissues were dissected and processed for histological paraffin embedding. Tissues were fixed in 4% glutaraldehyde solution and processed for ultrastructural analysis. Results: After EM, QG and HES treatment significantly increased the TAS and decreased the TOS value. EM caused epithelial and glandular degeneration, thinning of the basal membranes, and vascular dilatation with increased fibrosis and edema. QG+HES restored the pathology and showed protective effects in uterine tissues. Caspase-3 expression was increased in the epithelium, glands, and muscle layers of the EM group. In EM+QG+HES, hesperidin protected cell survival and decreased Caspase-3 expression in uterine tissues. TNF-α expression was intense in inflammatory cells and the muscle layer in the EM group. HES reduced inflammation by decreasing the TNF-α expression. MAPK expression was increased after EM induction in epithelial, glandular, and inflammatory cells in the EM group. After HES treatment, MAPK expression was mainly negative in cells of uterine tissue in the EM+QG+HES group. Ultrastructurally, in the EM group, organelles were disrupted and dilated and degenerated after EM induction. QG and HES treatment improved cellular organelles. Conclusion: Local vaginal applications can be an alternative treatment method in the endometriosis model via QG+HES treatment promoting cell proliferation and angiogenesis and preventing cell death. Full article

Nasal cytology is a non-invasive, low-cost exam that can help physicians in the diagnosis of allergic and nonallergic rhinitis, discriminating between different nasal disorders. The aim of this review is to summarize and analyze the current knowledge about nasal cytological examination in head and neck cancer, with a specific focus on the effects of different treatments. Indeed, nasal cytology is important to choose the best treatment for nasal complaints in each patient. A review of the English literature (PubMed, Scopus, Cochrane) was performed (5404 records screened). The inclusion criteria were clinical trials, cohort studies, case–control studies, case series, and case reports regarding nasal cytology in head and neck cancer treatment. Exclusion criteria were as follows: non-human studies, non-English literature, non-cytological evaluations. Two independent reviewers, working separately, extracted the data from all the eligible studies, which were subsequently cross-checked. Five studies were included in qualitative synthesis: three assessed mucosal disorders after radiation therapy and two after total laryngectomy. Radiotherapy can determine mucous or squamous cell metaplasia and neutrophil inflammation. Laryngectomees show hyperplasia of the basal zone cells and mucous cell metaplasia, and they do not develop inflammatory changes. The main limitation of this review is the low number and heterogeneity of studies present in the literature. In conclusion, nasal cytology is useful and allows for identifying mucosal disorders of the nasal cavities after surgery and/or radiotherapy for head and neck cancer. This can help physicians to better treat the nasal complaints of such patients. Full article